Scientists find resistance mechanism that could impact antibiotic drug development

Feb 20, 2014

Authors of the new study include (left to right) professor Ben Shen, research associate Jeffrey Rudolf and research associate Tingting Huang of the Scripps Research Institute. Credit: The Scripps Research Institute.

The use of antibiotics is often considered among the most important advances in the treatment of human disease. Unfortunately, though, bacteria are finding ways to make a comeback. According to the Centers for Disease Control, more than two million people come down with antibiotic-resistant infections annually, and at least 23,000 die because their treatment can't stop the infection. In addition, the pipeline for new antibiotics has grown dangerously thin.

Now, a new study by scientists from the Florida campus of The Scripps Research Institute (TSRI) has uncovered a mechanism of drug resistance. This knowledge could have a major impact on the development of a pair of highly potent new antibiotic drug candidates.

"Now, because we know the resistance mechanism, we can design elements to minimize the emergence of resistance as these promising new drug candidates are developed," said Ben Shen, a TSRI professor who led the study, which was published February 20, 2014 online ahead of print by the Cell Press journal Chemistry & Biology.

Bacteria Versus Bacteria

The study centers around a kind of bacteria known as Streptomyces platensis, which protects itself from other bacteria by secreting anti-bacterial substances. Interestingly, Streptomyces platensis belongs to a large family of antibiotic-producing bacteria that accounts for more than two-thirds of naturally occurring clinically useful antibiotics.

The antibiotic compounds secreted by Streptomyces platensis, which are called platensimycin and platencin and were discovered only recently, work by interfering with fatty acid synthesis. Fatty acid synthesis is essential for the production of bacterial cell walls and, consequently, the bacteria's existence. Platencin, although structurally similar to platensimycin, inhibits two separate enzymes in fatty acid synthesis instead of one.

The question remained, though, of why these compounds killed other bacteria, but not the producing bacteria Streptomyces platensis.

The Path to Resistance

The scientists set out to solve the mystery.

"Knowing how these bacteria protect themselves, what the mechanisms of self-resistance of the bacteria are, is important because they could transfer that resistance to other bacteria," said Tingting Huang, a research associate in the Shen laboratory who was first author of the study with Ryan M. Peterson of the University of Wisconsin, Madison.

Using genetic and bioinformatic techniques, the team identified two complementary mechanisms in the bacteria that confer resistance to platensimycin and platencin. In essence, the study found a pair of genes in Streptomyces platensis exploits a pathway to radically simplify fatty acid biosynthesis while bestowing an insensitivity to these particular antibiotics.

"Understanding how these elements work is a big leap forward," added Jeffrey D. Rudolf, a research associate in the Shen lab who worked on the study. "Now these bacteria have shown us how other bacteria might use this resistance mechanism to bypass fatty acid biosynthesis inhibition."

Related Stories

(PhysOrg.com) -- In recent years, scientists have isolated two potent natural antibiotics — platensimycin and platencin — that are highly effective against bacterial infection, including those caused by the most dreaded ...

The spread of multi-resistant pathogens is of increasing concern to medical researchers and laypeople alike. Yet it is expensive and time-consuming to develop new antibiotics. Researchers at the Universities of Tübingen ...

As more reports appear of a grim "post-antibiotic era" ushered in by the rise of drug-resistant bacteria, a new strategy for fighting infection is emerging that targets a patient's cells rather than those ...

A chemist based at the University of Copenhagen has just taken out a patent for a drug that can make previously multidrug-resistant bacteria once again responsive to antibiotics. Jørn Bolstad and his chemist ...

Recommended for you

(Phys.org)—As lithium resources continue to decline worldwide, the next generation of portable electronics will most likely be powered by something other than Li-ion batteries. One potential candidate is ...

Dislocations in oxides such as cerium dioxide, a solid electrolyte for fuel cells, turn out to have a property that is the opposite of what researchers had expected, according to a new analysis at MIT.

Cancer patients fear the possibility that one day their cells might start rendering many different chemotherapy regimens ineffective. This phenomenon, called multidrug resistance, leads to tumors that defy ...

A novel nucleating agent that builds on the concept of molecularly imprinted polymers (MIPs) could allow crystallographers access to proteins and other biological macromolecules that are usually reluctant ...

Researchers from institutions including Lund University have taken a step closer to producing solar fuel using artificial photosynthesis. In a new study, they have successfully tracked the electrons' rapid transit through ...

User comments : 0

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript.
In order to enable it, please see these instructions.